Sleep disturbances have profound and adverse affects on many aspects of society. Yet, the functions of sleep as well as the molecular causes of sleep remain poorly understood. The broad objective of this proposal is to study the role of feeding and interleukin-1(IL-1) in the regulation of sleep-wake activity. Most people subjectively recognize that sleep increases after feeding, after sleep deprivation or during the course of infectious disease. Indeed, manipulations which induce hyperphagia cause excess sleep whereas starvation results in decreased sleep. Further, there is a rapidly growing body of evidence implicating IL-1beta in sleep responses to infection, during sleep deprivation and in the regulation of physiological sleep. The proposed research seeks to understand: 1) The involvement of IL-Ibeta in sleep responses to feeding. The experiments will determine whether feeding-induced sleep can be mimicked by exogenous IL-1beta, whether feeding activates the IL-1 system in the liver and the brain by measuring IL-Ibeta mRNA and the IL-1 Type I receptor mRNA using RT-PCR, and whether the sleep responses to feeding can be attenuated by blocking the presumed source of IL-1beta, the liver Kupffer cells; and 2) The mechanism by which IL-1beta communicates sleep-promoting information to the brain. The experiments will determine whether vagotomy inhibits the sleep-inducing effects of IL-1beta as well as the activation of the Il-1 system in the brain. Knowledge of the molecular causes of sleep is likely to be a necessary step toward the understanding of sleep function; expected results will and this effort.